tbuckley/cabot-search huggingface dataset:
Contralateral Breast Cancer Risk Among Carriers of Germline Pathogenic Variants in <i>ATM</i>, <i>BRCA1</i>, <i>BRCA2</i>, <i>CHEK2</i>, and <i>PALB2</i>
Authors: Siddhartha Yadav, Nicholas J. Boddicker, Jie Na, Eric C. Polley, Chunling Hu, Steven N. Hart, Rohan D. Gnanaolivu, Nicole Larson, Susan Holtegaard, Huaizhi Huang, Carolyn A. Dunn, Lauren R. Teras, Alpa V. Patel, James V. Lacey, Susan L. Neuhausen, Elena Martinez, Christopher Haiman, Fei Chen, Kathryn J. Ruddy, Janet E. Olson, Esther M. John, Allison W. Kurian, Dale P. Sandler, Katie M. O'Brien, Jack A. Taylor, Clarice R. Weinberg, Hoda Anton-Culver, Argyrios Ziogas, Gary Zirpoli, David E. Goldgar, Julie R. Palmer, Susan M. Domchek, Jeffrey N. Weitzel, Katherine L. Nathanson, Peter Kraft, Fergus J. Couch
Journal: Journal of Clinical Oncology (2023)

PURPOSE To estimate the risk of contralateral breast cancer (CBC) among women with germline pathogenic variants (PVs) in ATM, BRCA1, BRCA2, CHEK2, and PALB2. METHODS The study population included 15,104 prospectively followed women within the CARRIERS study treated with ipsilateral surgery for invasive breast cancer. The risk of CBC was estimated for PV carriers in each gene compared with women without PVs in a multivariate proportional hazard regression analysis accounting for the competing risk of death and adjusting for patient and tumor characteristics. The primary analyses focused on the overall cohort and on women from the general population. Secondary analyses examined associations by race/ethnicity, age at primary breast cancer diagnosis, menopausal status, and tumor estrogen receptor (ER) status. RESULTS Germline BRCA1, BRCA2, and CHEK2 PV carriers with breast cancer were at significantly elevated risk (hazard ratio &gt; 1.9) of CBC, whereas only the PALB2 PV carriers with ER-negative breast cancer had elevated risks (hazard ratio, 2.9). By contrast, ATM PV carriers did not have significantly increased CBC risks. African American PV carriers had similarly elevated risks of CBC as non-Hispanic White PV carriers. Among premenopausal women, the 10-year cumulative incidence of CBC was estimated to be 33% for BRCA1, 27% for BRCA2, and 13% for CHEK2 PV carriers with breast cancer and 35% for PALB2 PV carriers with ER-negative breast cancer. The 10-year cumulative incidence of CBC among postmenopausal PV carriers was 12% for BRCA1, 9% for BRCA2, and 4% for CHEK2. CONCLUSION Women diagnosed with breast cancer and known to carry germline PVs in BRCA1, BRCA2, CHEK2, or PALB2 are at substantially increased risk of CBC and may benefit from enhanced surveillance and risk reduction strategies.
Idecabtagene Vicleucel for Relapsed/Refractory Multiple Myeloma: Real-World Experience From the Myeloma CAR T Consortium
Authors: Doris K. Hansen, Surbhi Sidana, Lauren C. Peres, Christelle Colin Leitzinger, Leyla Shune, Alexandria Shrewsbury, Rebecca Gonzalez, Douglas W. Sborov, Charlotte Wagner, Danai Dima, Hamza Hashmi, Mehmet H. Kocoglu, Shebli Atrash, Gary Simmons, Nilesh Kalariya, Christopher Ferreri, Aimaz Afrough, Ankit Kansagra, Peter Voorhees, Rachid Baz, Jack Khouri, Melissa Alsina, Joseph McGuirk, Frederick L. Locke, Krina K. Patel
Journal: Journal of Clinical Oncology (2023)

Idecabtagene vicleucel (ide-cel) is an autologous B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy approved for relapsed/refractory multiple myeloma (RRMM) on the basis of the phase II pivotal KarMMa trial, which demonstrated best overall and ≥ complete response rates of 73% and 33%, respectively. We report clinical outcomes with standard-of-care (SOC) ide-cel under the commercial Food and Drug Administration label.
Decoding semantic representations in mind and brain
Authors: Saskia L. Frisby, Ajay D. Halai, Christopher R. Cox, Matthew A. Lambon Ralph, Timothy T. Rogers
Journal: Trends in Cognitive Sciences (2023)

A key goal for cognitive neuroscience is to understand the neurocognitive systems that support semantic memory. Recent multivariate analyses of neuroimaging data have contributed greatly to this effort, but the rapid development of these novel approaches has made it difficult to track the diversity of findings and to understand how and why they sometimes lead to contradictory conclusions. We address this challenge by reviewing cognitive theories of semantic representation and their neural instantiation. We then consider contemporary approaches to neural decoding and assess which types of representation each can possibly detect. The analysis suggests why the results are heterogeneous and identifies crucial links between cognitive theory, data collection, and analysis that can help to better connect neuroimaging to mechanistic theories of semantic cognition.
SARS-CoV-2 diagnostic testing rates determine the sensitivity of genomic surveillance programs
Authors: Alvin X. Han, Amy Toporowski, Jilian A. Sacks, Mark D. Perkins, Sylvie Briand, Maria van Kerkhove, Emma Hannay, Sergio Carmona, Bill Rodriguez, Edyth Parker, Brooke E. Nichols, Colin A. Russell
Journal: Nature Genetics (2023)

The first step in SARS-CoV-2 genomic surveillance is testing to identify people who are infected. However, global testing rates are falling as we emerge from the acute health emergency and remain low in many low- and middle-income countries (mean = 27 tests per 100,000 people per day). We simulated COVID-19 epidemics in a prototypical low- and middle-income country to investigate how testing rates, sampling strategies and sequencing proportions jointly impact surveillance outcomes, and showed that low testing rates and spatiotemporal biases delay time to detection of new variants by weeks to months and can lead to unreliable estimates of variant prevalence, even when the proportion of samples sequenced is increased. Accordingly, investments in wider access to diagnostics to support testing rates of approximately 100 tests per 100,000 people per day could enable more timely detection of new variants and reliable estimates of variant prevalence. The performance of global SARS-CoV-2 genomic surveillance programs is fundamentally limited by access to diagnostic testing.
The risk of methicillin-resistant Staphylococcus aureus infection following COVID-19 and influenza: A retrospective cohort study from the TriNetX network
Authors: Ya-Wen Tsai, Chia-Fen Tsai, Jheng-Yan Wu, Po-Yu Huang, Ting-Hui Liu, Chih-Cheng Lai
Journal: Journal of Infection (2023)
Single-cell transcriptomics unveils xylem cell development and evolution
Authors: Chia-Chun Tung, Shang-Che Kuo, Chia-Ling Yang, Jhong-He Yu, Chia-En Huang, Pin-Chien Liou, Ying-Hsuan Sun, Peng Shuai, Jung-Chen Su, Chuan Ku, Ying-Chung Jimmy Lin
Journal: Genome biology (2023)

Abstract Background Xylem, the most abundant tissue on Earth, is responsible for lateral growth in plants. Typical xylem has a radial system composed of ray parenchyma cells and an axial system of fusiform cells. In most angiosperms, fusiform cells comprise vessel elements for water transportation and libriform fibers for mechanical support, while both functions are performed by tracheids in other vascular plants such as gymnosperms. Little is known about the developmental programs and evolutionary relationships of these xylem cell types. Results Through both single-cell and laser capture microdissection transcriptomic profiling, we determine the developmental lineages of ray and fusiform cells in stem-differentiating xylem across four divergent woody angiosperms. Based on cross-species analyses of single-cell clusters and overlapping trajectories, we reveal highly conserved ray, yet variable fusiform, lineages across angiosperms. Core eudicots Populus trichocarpa and Eucalyptus grandis share nearly identical fusiform lineages, whereas the more basal angiosperm Liriodendron chinense has a fusiform lineage distinct from that in core eudicots. The tracheids in the basal eudicot Trochodendron aralioides , an evolutionarily reversed trait, exhibit strong transcriptomic similarity to vessel elements rather than libriform fibers. Conclusions This evo-devo framework provides a comprehensive understanding of the formation of xylem cell lineages across multiple plant species spanning over a hundred million years of evolutionary history.
Implantation underneath the abdominal anterior rectus sheath enables effective and functional engraftment of stem-cell-derived islets
Authors: Zhen Liang, Dong Sun, Shuaiyao Lu, Zhengjun Lei, Shusen Wang, Zhifeng Luo, Jinqin Zhan, Shuangshuang Wu, Yong Jiang, Zhi Lu, Shicheng Sun, Yingying Shi, Haiting Long, Yanling Wei, Wenhai Yu, Zhihui Wang, Liew Soon Yi, Yun Zhang, Wenyong Sun, Xiaofeng Fang, Yanyan Li, Sufang Lu, Jiayun Lv, Weiguo Sui, Zhongyang Shen, Xiaozhong Peng, Yuanyuan Du, Hongkui Deng
Journal: Nature Metabolism (2023)
Autologous T cell therapy for MAGE-A4+ solid cancers in HLA-A*02+ patients: a phase 1 trial
Authors: David S. Hong, Brian A. Van Tine, Swethajit Biswas, Cheryl McAlpine, Melissa L. Johnson, Anthony J. Olszanski, Jeffrey M. Clarke, Dejka Araujo, George R. Blumenschein, Partow Kebriaei, Quan Lin, Alex J. Tipping, Joseph P. Sanderson, Ruoxi Wang, Trupti Trivedi, Thejo Annareddy, Jane Bai, Stavros Rafail, Amy Sun, Lilliam Fernandes, Jean-Marc Navenot, Frederic D. Bushman, John K. Everett, Derin Karadeniz, Robyn Broad, Martin Isabelle, Revashnee Naidoo, Natalie Bath, Gareth Betts, Zohar Wolchinsky, Dzmitry G. Batrakou, Erin Van Winkle, Erica Elefant, Armin Ghobadi, Amanda Cashen, Anne Grand’Maison, Philip McCarthy, Paula M. Fracasso, Elliot Norry, Dennis Williams, Mihaela Druta, David A. Liebner, Kunle Odunsi, Marcus O. Butler
Journal: Nature Medicine (2023)

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced Grade ≥3 hematologic toxicities; 55% of patients (90% Grade ≤2) experienced cytokine release syndrome. ORR (all partial response) was 24% (9/38), 7/16 (44%) for SS and 2/22 (9%) for all other cancers. Median duration of response was 25.6 weeks (95% confidence interval (CI): 12.286, not reached) and 28.1 weeks (95% CI: 12.286, not reached) overall and for SS, respectively. Exploratory analyses showed that afami-cel infiltrates tumors, has an interferon-γ-driven mechanism of action and triggers adaptive immune responses. In addition, afami-cel has an acceptable benefit-risk profile, with early and durable responses, especially in patients with metastatic SS. Although the small trial size limits conclusions that can be drawn, the results warrant further testing in larger studies.
NgR1 is an NK cell inhibitory receptor that destabilizes the immunological synapse
Authors: Se-Chan Oh, Seong-Eun Kim, In-Hwan Jang, Seok-Min Kim, Soo Yun Lee, Sunyoung Lee, In-Sun Chu, Suk Ran Yoon, Haiyoung Jung, Inpyo Choi, Junsang Doh, Tae-Don Kim
Journal: Nature Immunology (2023)
Risk of infections in patients with pemphigus treated with rituximab vs. azathioprine or mycophenolate mofetil: a large-scale global cohort study
Authors: Khalaf Kridin, Noor Mruwat, Kyle T Amber, Ralf J Ludwig
Journal: British Journal of Dermatology (2023)

Abstract Background The risk of infectious complications among patients with pemphigus managed by rituximab is yet to be precisely elucidated. Objectives To evaluate the risk of infections in patients with pemphigus managed by rituximab vs. first-line corticosteroid-sparing agents [azathioprine and mycophenolate mofetil (MMF)]. Methods A global population-based cohort study compared patients with pemphigus initiating rituximab (n = 963) vs. azathioprine or MMF (n = 963) regarding the risk of 26 different infections. Propensity score matching was conducted to optimize comparability. Results During the initial 12 months following treatment, patients under rituximab experienced elevated risk of COVID-19 [hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.06–3.14; P = 0.028], parasitic diseases (HR 3.22, 95% CI 1.04–9.97; P = 0.032) and cytomegalovirus (CMV) infection (HR 1.63, 95% CI 1.04–2.58; P = 0.033). When evaluating infections developing ≥ 12 months after drug initiation, rituximab was associated with greater risk of pneumonia (HR 1.45, 95% CI 1.00–2.10; P = 0.047), COVID-19 (HR 1.87, 95% CI 1.49–2.33; P &amp;lt; 0.001), osteomyelitis (HR 2.42, 95% CI 1.11–5.31; P = 0.023), herpes simplex virus (HR 2.06, 95% CI 1.03–4.11; P = 0.037) and CMV (HR 1.63, 95% CI 1.07–2.49; P = 0.023) infections. Conclusions Within the first 12 months after treatment, patients under rituximab experience an elevated risk of COVID-19, parasitic and CMV infections. Rituximab is associated with pneumonia, osteomyelitis and viral diseases even beyond the first year after therapy. Pneumococcal vaccine and suppressive antiviral therapy should be considered even 1 year following therapy. There is no signal for elevated risk of tuberculosis, hepatitis B virus reactivation, Pneumocystis jiroveci pneumonia and progressive multifocal leukoencephalopathy.
The age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques
Authors: Inamul Kabir, Xinbo Zhang, Jui M. Dave, Raja Chakraborty, Rihao Qu, Rachana R. Chandran, Aglaia Ntokou, Eunate Gallardo-Vara, Binod Aryal, Noemi Rotllan, Rolando Garcia-Milian, John Hwa, Yuval Kluger, Kathleen A. Martin, Carlos Fernández-Hernando, Daniel M. Greif
Journal: Nature Aging (2023)
Employing Macrophage-Derived Microvesicle for Kidney-Targeted Delivery of Dexamethasone: An Efficient Therapeutic Strategy against Renal Inflammation and Fibrosis: Erratum
Authors: Tao-Tao Tang, Lin-Li Lv, Bin Wang, Jing-Yuan Cao, Ye Feng, Zuo-Lin Li, Min Wu, Feng-Mei Wang, Yi Wen, Le-Ting Zhou, Hai-Feng Ni, Ping-Sheng Chen, Ning Gu, Steven D. Crowley, Bi-Cheng Liu
Journal: Theranostics (2023)

[This corrects the article DOI: 10.7150/thno.33520.].
TCRαβ<sup>+</sup>NK1.1<sup>-</sup>CD4<sup>-</sup>CD8<sup>-</sup> double-negative T cells inhibit central and peripheral inflammation and ameliorate ischemic stroke in mice
Authors: Dan Tian, Yuhualei Pan, Yushang Zhao, Huan Wang, Yue Tian, Lu Yang, Wen Shi, Chengjie Zhang, Yanbing Zhu, Yongbo Zhang, Songlin Wang, Dong Zhang
Journal: Theranostics (2023)

Background: Excessive immune activation leads to secondary injury and impedes injured brain recovery after ischemic stroke.However, few effective methods are currently used for equilibrating immune balance.CD3 + NK1.1 -TCRβ + CD4 -CD8 -double-negative T (DNT) cells which do not express NK cell surface markers are unique regulatory cells that maintain homeostasis in several immune-related diseases.However, the therapeutic potential and regulatory mechanism of DNT cells in ischemic stroke are still unknown.Methods: Mouse ischemic stroke is induced by occlusion of the distal branches of the middle cerebral artery (dMCAO).DNT cells were adoptively transferred intravenously into ischemic stroke mice.Neural recovery was evaluated by TTC staining and behavioral analysis.Using immunofluorescence, flow cytometry, and RNA sequencing, the immune regulatory function of DNT cells was investigated at different time points post ischemic stroke.Results: Adoptive transfer of DNT cells significantly reduces infarct volume and improves sensorimotor function after ischemic stroke.DNT cells suppress peripheral Trem1 + myeloid cell differentiation during the acute phase.Furthermore, they infiltrate the ischemic tissue via CCR5 and equilibrate the local immune balance during the subacute phase.During the chronic phase, DNT cells enhance Treg cell recruitment through CCL5, eventually developing an immune homeostatic milieu for neuronal recovery.Conclusions: DNT cell treatment renders the comprehensive anti-inflammatory roles in specific phases of ischemic stroke.Our study suggests that the adoptive transfer of regulatory DNT cells may be a potential cell-based therapy for ischemic stroke.
Young Bone Marrow Sca-1 Cells Rejuvenate the Aged Heart by Promoting Epithelial-to-Mesenchymal Transition: Erratum
Authors: Jiao Li, Shu-Hong Li, Jun Wu, Richard D. Weisel, Alina Yao, William L. Stanford, Shi-Ming Liu, Ren-Ke Li
Journal: Theranostics (2023)

[This corrects the article DOI: 10.7150/thno.22788.].
NQO1 regulates cell cycle progression at the G2/M phase
Authors: Eun-Taex Oh, Ha Gyeong Kim, Chul Hoon Kim, Jeonghun Lee, Chulhee Kim, Jae-Seon Lee, Yunmi Cho, Heon Joo Park
Journal: Theranostics (2023)

Rationale: Overexpression of NAD(P)H:quinone oxidoreductase 1 (NQO1) is associated with tumor cell proliferation and growth in several human cancer types. However, the molecular mechanisms underlying the activity of NQO1 in cell cycle progression are currently unclear. Here, we report a novel function of NQO1 in modulation of the cell cycle regulator, cyclin-dependent kinase subunit-1 (CKS1), at the G2/M phase through effects on the stability of c‑Fos. Methods: The roles of the NQO1/c-Fos/CKS1 signaling pathway in cell cycle progression were analyzed in cancer cells using synchronization of the cell cycle and flow cytometry. The mechanisms underlying NQO1/c-Fos/CKS1-mediated regulation of cell cycle progression in cancer cells were studied using siRNA approaches, overexpression systems, reporter assays, co-immunoprecipitation, pull-down assays, microarray analysis, and CDK1 kinase assays. In addition, publicly available data sets and immunohistochemistry were used to investigate the correlation between NQO1 expression levels and clinicopathological features in cancer patients. Results: Our results suggest that NQO1 directly interacts with the unstructured DNA-binding domain of c-Fos, which has been implicated in cancer proliferation, differentiation, and development as well as patient survival, and inhibits its proteasome-mediated degradation, thereby inducing CKS1 expression and regulation of cell cycle progression at the G2/M phase. Notably, a NQO1 deficiency in human cancer cell lines led to suppression of c-Fos-mediated CKS1 expression and cell cycle progression. Consistent with this, high NQO1 expression was correlated with increased CKS1 and poor prognosis in cancer patients. Conclusions: Collectively, our results support a novel regulatory role of NQO1 in the mechanism of cell cycle progression at the G2/M phase in cancer through effects on c‑Fos/CKS1 signaling.
STAT3 mutation-associated airway epithelial defects in Job syndrome
Authors: Yihan Zhang, Tian Lin, Hui Min Leung, Cheng Zhang, Brittany Wilson-Mifsud, Michael B. Feldman, Anne Puel, Fanny Lanternier, Louis-Jean Couderc, Francois Danion, Emilie Catherinot, Hélène Salvator, Colas Tcherkian, Claire Givel, Jie Xu, Guillermo J. Tearney, Jatin M. Vyas, Hu Li, Bryan P. Hurley, Hongmei Mou
Journal: Journal of Allergy and Clinical Immunology (2023)
Recent advances in the pathogenesis and clinical assessment of mineral dust pneumoconioses: asbestosis, silicosis and coal pneumoconiosis
Authors: R Begin, A Cantin, S Masse
Journal: European Respiratory Journal (1989)

Recent investigations of the fundamental mechanisms of the mineral dust diseases have substantially increased our understanding of the pathogenesis of the pneumoconioses. In all the mineral dust pneumoconioses, the initial early lung lesion is a fibrosing macrophagic alveolitis. The additional contribution of other lung cell populations is currently under investigation and may identify specific processes for each of the pneumoconioses. Clinical investigations have also progressed with new tools such as Gallium-67 lung scanning, bronchoalveolar lavage analyses, and CT scanning of the thorax; their established values are reviewed in this paper, and areas where progress is needed are considered. The clinical progress in the mineral dust diseases is clearly linked to the basic understanding of the mechanisms of these diseases.
The Cynosure of CtBP: Evolution of a Bilaterian Transcriptional Corepressor
Authors: Ana-Maria Raicu, Dhruva Kadiyala, Madeline Niblock, Aanchal Jain, Yahui Yang, Kalynn M Bird, Kayla Bertholf, Akshay Seenivasan, Mohammad Siddiq, David N Arnosti
Journal: Molecular Biology and Evolution (2023)

Evolution of sequence-specific transcription factors clearly drives lineage-specific innovations, but less is known about how changes in the central transcriptional machinery may contribute to evolutionary transformations. In particular, transcriptional regulators are rich in intrinsically disordered regions that appear to be magnets for evolutionary innovation. The C-terminal Binding Protein (CtBP) is a transcriptional corepressor derived from an ancestral lineage of alpha hydroxyacid dehydrogenases; it is found in mammals and invertebrates, and features a core NAD-binding domain as well as an unstructured C-terminus (CTD) of unknown function. CtBP can act on promoters and enhancers to repress transcription through chromatin-linked mechanisms. Our comparative phylogenetic study shows that CtBP is a bilaterian innovation whose CTD of about 100 residues is present in almost all orthologs. CtBP CTDs contain conserved blocks of residues and retain a predicted disordered property, despite having variations in the primary sequence. Interestingly, the structure of the C-terminus has undergone radical transformation independently in certain lineages including flatworms and nematodes. Also contributing to CTD diversity is the production of myriad alternative RNA splicing products, including the production of "short" tailless forms of CtBP in Drosophila. Additional diversity stems from multiple gene duplications in vertebrates, where up to five CtBP orthologs have been observed. Vertebrate lineages show fewer major modifications in the unstructured CTD, possibly because gene regulatory constraints of the vertebrate body plan place specific constraints on this domain. Our study highlights the rich regulatory potential of this previously unstudied domain of a central transcriptional regulator.